Patient-ventilator synchrony is a major concern in critical care and is influenced by phasic lung-volume feedback control of the respiratory rhythm. Routine clinical application of positive end-expiratory pressure (PEEP) introduces a tonic input which, if unopposed, might disrupt respiratory-ventilator entrainment through sustained activation of the vagally-mediated Hering-Breuer reflex.
Mechanically ventilated patients in critical care who are unable to entrain their respiratory activity to the ventilator rhythm and who instead fight the ventilator often require sedation or even paralysis in order to avoid lung injury and improve pulmonary ventilation (M. J. Tobin, C. Alex, and P. J. Fahey “Fighting the ventilator,” Principles and Practice of Mechanical Ventilation, pp. 1121-1136, McGraw-Hill, 2006). Patient-ventilator interaction is a complex process that is determined not only by the clinician-prescribed ventilator settings but also the patient's moment-to-moment reaction to the ventilator-delivered breath (C. R. Dick and C. S. Sassoon, “Patient-ventilator interactions,” Clinical Chest Medicine 17: 423-438, 1996; E. Kondili, G. Prinianakis, and D. Georgopoulos, “Patient-ventilator interaction,” British Journal of Anesthesia, 91: 106-119, 2003; M. J. Tobin, A. Jubran, and f. Laghi, “Patient-ventilator interaction,” American Journal Respiratory and Critical Care Medicine, 163: 1059-1063, 2001; M. J. Tobin, “Advances in mechanical ventilation,” New England Journal of Medicine, 344: 1986-1996, 2001). Although synchrony may be improved with the use of various patient-triggered ventilatory assist modes (C. S. Poon, H. H. Lebowitz, D. A. Sidney, and S. X. Li, “Negative-impedance ventilation and pressure support ventilation: a comparative study,” Respiratory Physiology, 108: 117-127, 1997; C. Sinderby, P. Navalesi, J. Beck, Y. Skrobik, and N. Comtois, et al., “Neural control of mechanical ventilation in respiratory failure,” Nature Medicine, 5: 1433-1436, 1999; T. Sharshar, G. Desmarais, B. Louis, G. Macadou, and R. Porcher, et al., “Transdiaphragmatic pressure control of airway pressure support in healthy subjects,” American Journal of Respiratory and Critical Care Medicine, 168: 760-769, 2003) the latter are relatively complex, costly, and not always feasible or beneficial especially in neonates (M. W. Beresford, N. J. Shaw, and D. Manning “Randomized controlled trial of patient triggered and conventional fast rate ventilation in neonatal respiratory distress syndrome,” Archive of Disease in Childhood Fetal Neonatal, Edition 82: F14-18, 2000; J. H. Baumer, “International randomized controlled trial of patient triggered ventilation in neonatal respiratory distress syndrome,” Archive of Disease in Childhood Fetal Neonatal, Edition 82: F5-F10, 2000) or during prolonged mechanical ventilation (A. W Thille, P. Rodriguez, B. Cabello, F. Lellouche, and L. Brochard, “Patient-ventilator asynchrony during assisted mechanical ventilation,” Intensive Care Medicine, 32: 1515-1522, 2006; D. C. Chao, D. J. Scheinhorn, and M. Stearn-Hassenpflug, “Patient-ventilator trigger asynchrony in prolonged mechanical ventilation,” Chest, 112: 1592-1599, 1997), and may be prone to auto-triggering (H. Imanaka, M. Nishimura, M. Takeuchi, W. R. Kimball, and N. Yahagi, et al., “Auto triggering caused by cardiogenic oscillation during flow-triggered mechanical ventilation,” Critical Care Medicine, 28: 402-407, 2000). Further complicating this process is the inevitable presence of extrinsic and/or intrinsic (auto) positive end-expiratory pressure (PEEP) (M. Oddo, F. Feihi, M. D. Schaller, and C. Perret, “Management of mechanical ventilation in acute severe asthma: practical aspects,” intensive Care Medicine, 32: 501-510, 2006; P. E Pepe, and J. J Marini, “Occult positive end-expiratory pressure in mechanically ventilated patients with airflow obstruction: the auto-PEEP effect,” American Review of Respiratory Disease, 126: 166-170, 1982; L. Brochard, “Intrinsic (or auto-) PEEP during controlled mechanical ventilation,” Intensive Care Medicine, 28: 1376-1378, 2002), which may significantly influence the spontaneous breathing pattern (C. Haberthur, and J. Guttmann, “Short-term effects of positive end-expiratory pressure on breathing pattern: an interventional study in adult intensive care patients,” Critical Care, 9: R407-415, 2005) and hence, patient-ventilator synchrony.
The rising popularity of patient-triggered assisted ventilation is premised on the general belief that patient-ventilator synchrony is difficult if not impossible with controlled (non-patient triggered) mechanical ventilation. On the contrary, many studies in anesthetized animals or awake or sleeping humans have shown that periodic lung inflation during controlled mechanical ventilation may entrain the respiratory rhythm to the ventilation frequency or some sub-harmonics close to the intrinsic respiratory frequency (G. A. Petrillo, L. Glass, and T. Trippenbach, “Phase locking of the respiratory rhythm in cats to a mechanical ventilator,” Canadian Journal of Physiology and Pharmacology, 61: 599-607, 1983; C. Graves, L. Glass, D. Laporta, R. Meloche, and A. Grassino, “Respiratory phase locking during mechanical ventilation in anesthetized human subjects,” American Journal of Physiology, 250: R902-909, 1986; S. Muzzin, P Baconnier, and G Benchetrit, “Entrainment of respiratory rhythm by periodic lung inflation: effect of airflow rate and duration,” American Journal of Physiology, 263: R292-300, 1992; P. M. Simon, A. S. Zurob, W. M. Wies, J. C. Leiter, and R. D. Hubmayr, “Entrainment of respiration in humans by periodic lung inflations. Effect of state and CO(2),” American Journal of Respiratory and Critical Care Medicine, 160: 950-960, 1999; P. M. Simon, A. M. Habel, J. A. Daubenspeck, and J. C. Leiter, “Vagal feedback in the entrainment of respiration to mechanical ventilation in sleeping humans,” Journal of Applied Physiology, 89: 760-769, 2000; P. F. Baconnier, G. Benchetrit, P. Pachot, and J. Demongeot, “Entrainment of the respiratory rhythm: a new approach,” Journal of Theoretical Biology, 164: 149-162, 1993). The ratio of the respiratory frequency and ventilation frequency, termed the rotation number, is a measure of the relative strength of the entrainment, where the strongest ratio is 1:1 (P. F. Baconnier, G. Benchetrit, P. Pachot, and J. Demongeot, “Entrainment of the respiratory rhythm: a new approach,” Journal of Theoretical Biology, 164: 149-162, 1993; J. F. Vibert, D. Caille, and J. P. Segundo, “Respiratory oscillator entrainment by periodic vagal afferentes: an experimental test of a model,” Biological Cybernetic, 41: 19-130, 1981; G. A. Petrillo, and L. Glass, “A theory for phase locking of respiration in cats to a mechanical ventilator,” American Journal of Physiology, 246: R311-320, 1984; M. Matsugu, J. Duffin, and C. S. Poon, “Entrainment, instability, quasi-periodicity, and chaos in a compound neural oscillator,” Journal of Computational Neuroscience, 5: 35-51, 1998). In anesthetized animals such entrainment is abolished after bilateral vagotomy (J. F. Vibert, D. Caille, and J. P. Segundo, “Respiratory oscillator entrainment by periodic vagal afferentes: an experimental test of a model,” Biological Cybernetic, 41: 119-130, 1981; G. A. Petrillo, and L. Glass, “A theory for phase locking of respiration in cats to a mechanical ventilator,” American Journal of Physiology, 246: R311-320, 1984) and impaired after vagal cooling (S. Muzzin, T. Trippenbach, P. Baconnier, and G. Benchetrit, “Entrainment of the respiratory rhythm by periodic lung inflation during vagal cooling,” Respiratory Physiology, 75: 157-172, 1998) indicating that it is mediated primarily by pulmonary slowly adapting stretch receptors and secondarily by pulmonary rapidly adapting receptors and/or vagal C-fibers.